P570: VENETOCLAX PLUS HYPOMETHYLATING AGENTS VERSUS INTENSIVE CHEMOTHERAPY FOR HEMATOLOGICAL RELAPSE OF MYELOID MALIGNANCIES AFTER ALLO-HSCT
Authors: Zhangjie Chen, Sisi Zhen, Xin Chen, Sizhou Feng
Journal: HemaSphere (2023)

Background: Since allogeneic stem cell transplantation (allo-HSCT) is considered one of the curative treatments for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), hematological relapse following allo-HSCT remained a crucial concern for patients’ survival. Recent studies have demonstrated the impressive efficacy of venetoclax plus intensive chemotherapy for newly diagnosed and relapsed/refractory (R/R) AML. However, its safety and effectiveness compared to other regimens in post-transplantation relapse has yet to be determine. Aims: In this retrospective study, we investigated 65 patients treated with either venetoclax plus hypomethylating agents (VEN+HMA) (n=23) or intensive chemotherapy (IC) (n=42) for hematological relapsed myeloid malignancies after allo-HSCT and compared response, survival, graft-versus-host disease (GvHD) and adverse events between the two regimens. Methods: The study included 23 patients who received VEN+HMA and 42 patients who received IC after relapse of myeloid malignancies. In VEN+HMA group, twenty-one patients received azacitidine and 2 patients used decitabine in combination with venetoclax. In IC group, IDAC (n=15), FLAG (n=16) and CLAG (n=11) were used. Donor lymphocyte infusion was administered in 21 and 42 patients in VEN+HMA and IC groups, respectively. The response rate, adverse effects and GvHD were recorded and compared. Overall survival was compared using Kaplan-Meier method, predictors were calculated via Cox regression model. Results: Median age of all patients was 39 (16-64) years old. No significant differences were observed between VEN+HMA and IC groups concerning age, gender, initial disease types, risk stratification, therapies before allo-HSCT, donor types and disease status at transplantation. In VEN+HMA group, twelve patients (52.2%) achieved CR/CRi (CR=2, CRi=10), with 4 patients (17.4%) reaching MRD negativity. However, eight of the 12 CR/CRi patients (66.7%) relapsed later. In the IC group, twenty-five (59.5%) patients achieved CR/CRi (CR=8, CRi=17), and 12 patients (28.6%) achieved MRD negativity. Eleven of the 25 patients (40.7%) who responded later relapsed. No statistical significance was observed between two groups regarding response, relapse after response, treatment-related mortality and early mortality. Median OS was 209 days for VEN+HMA group and 211 days for IC group (P=0.491). Multivariable analysis identified that male gender, FLT3-ITD mutation, concomitant pulmonary infection at relapse, late-onset relapse, treatment-induced grade III/IV aGvH and WBC>10,000/microL at relapse significantly impacted survival. Thrombocytopenia was the most common event in both treatment groups, but the incidence was significantly higher in IC group than in VEN+HMA group (95.2% versus 73.9%, P=0.035). And pneumonia was the most common infection, with a significant higher incidence rate in IC group (50.0% versus 17.4%, P=0.010). Notably, aGvHD incidence after relapse treatment was significantly lower in VEN+HMA group (13.0% versus 50.0% in IC group, P=0.003). Summary/Conclusion: This retrospective study demonstrated that compared to intensive chemotherapy, venetoclax plus hypomethylating agents is an effective and safe regimen for hematological relapse of myeloid malignancies after allo-HSTC. Nevertheless, prospective researches and clinical trials are necessary to verify results, and more detailed exploration is required for maintenance therapy in responders.Overall survival of patients receiving venetoclax-based treatment vs. IC treatment. Keywords: Acute myeloid leukemia, Allogeneic hematopoietic stem cell transplant, Venetoclax, Relapsed acute myeloid leukemia